The computational analysis of human testis transcriptome reveals closer ties to pluripotency

AIMS: The purpose of this study was to identify the differentially expressed genes (DEG) in human testis and also evaluate the relationship between human testis, human Embryonic Stem Cells (hESC), mouse testis and mouse ESCs (mESC). SETTINGS AND DESIGN: It is a prospective analysis designed computationally. Methods and Material: The microarray data for human testis, hESCs, mouse testis and mESCs were obtained from NCBI-GEO and analyzed for identification of DEGs. The results were then compared with mouse testis and extended to ESCs. STATISTICAL ANALYSIS USED: Data was analyzed in R using various Bioconductor packages. To identify DEGs, 2-fold cut-off and a False Discovery Rate (FDR) below 0.01 criterions was used. RESULTS: A total 2868 transcripts (DEGs) were found to be significantly up-regulated and 2011 transcripts significantly down-regulated in human testis compared to other normal tissues. Of the up-regulated transcripts, 232 transcripts were grouped as unclassified i.e. had unknown annotations at the time of analysis. Gene Ontology (GO) based functional annotation of testis specific DEGs indicate that most of the DEGs (~80%) are involved in various metabolic processes. Pathway analysis shows over-representation of Ubiquitin-mediated proteolysis pathway. A core group of 67 transcripts were found to be common among human testis, mouse testis, hESCs and mESCs. CONCLUSIONS: Testis seems to be metabolically very active relative to other normal tissues as indicated by functional annotation. The comparison of human and mouse testis shows conserved functions and pathways involved in both species. Large numbers of genes were found conserved between testis and ESCs suggesting very close expression level relationship between reproductive organs and complex phenomenon such as dedifferentiation and reprogramming.